1. Field of the Invention
The invention relates to computer implemented molecular modeling tools and the display of molecular structures to a user.
2. Description of the Related Art
Chemists often find it desirable to visualize the structure of molecules in two or three dimensions. In rational drug design applications, for example, functional interactions between proteins and ligands can be illustrated by an analysis of the three dimensional structure of the two molecules. Protein-ligand binding sites, for example, may be discovered using such three dimensional models. Although such models were originally done with physical ball-and-stick or space filling kits, computer programs and high resolution graphic displays have become regularly used for the visualization of multidimensional molecular models. With these programs, a chemist can input a selected set of atoms and their bonds, thereby defining a molecular structure for display and analysis.
Originally, these computer programs were used mainly by highly trained computational chemists that specialized in the use of computer models to understand and predict chemical behavior. Over the past several years, however, bench chemists, biologists, and other researchers that work predominantly in the wet laboratory environment have begun to utilize computer modeling techniques to a much greater extent. This development has spurred the need to provide molecular modeling tools which are more user friendly than those previously available in the past.
In some currently available computer modeling programs, the physical validity of a molecular structure is evaluated automatically. It is well known to those in the art that one important aspect of the physical validity of a given molecular model is the satisfaction of the valences for each atom of the molecule. For example, the orbital configuration of the four valence shell electrons in carbon define a set of covalent bond structures for this element. Each of these configurations requires a total of four bonds between a given carbon and its covalently bonded partners to satisfy the valence of a given carbon atom. Similar considerations are present for other elements. Oxygen, for example requires two bonds for valence satisfaction.
With validity checking features as part of a molecular modeling program, the user may receive information from the program indicating whether or not a given atom has under or over filled valences. This feature may take a number of forms. In some programs, the user may select an atom, and a text window is displayed which includes an indication of the atom""s valence status. If desired, the user may then close the text window and return to the molecular design algorithm to correct any problems set forth therein.
In a program commercially available under the name ISIS Draw(trademark), from MDL Information Systems Inc., the user is informed when an over valence condition is about to be created during the process of designing the molecular structure. The user is then given the option to either refrain from placing the bond which will create the over valence condition, or to disable the validity checking from that atom. In the latter case, no further warnings are delivered to the user if additional bonds are made to the already over hybridized atom. ISIS Draw(trademark) can also check the structure with a separate subroutine after the drawing is complete. This subroutine informs the user of problems, but does not identify the invalid atoms.
In a web-based program called Test Grins, available from Daylight Chemical Information Systems, Inc., the user first types a desired structure, and then runs a separate subroutine which checks the structure for over and under valenced atoms. The user may then return to the molecular design algorithm, and correct the problem atoms and/or bonds if desired.
In another program called CS ChemDraw, available from CambridgeSoft, the user can check the structure with a separate subroutine after the drawing is complete. This subroutine indicates problems with the molecular structure by highlighting one atom at a time.
In each of these cases, the information provided to the user is in a format which is relatively difficult to access and use, and in some cases does not indicate the portion of the molecular structure that is incorrect. Instant availability of information relating to the validity status of the atoms of a molecule being designed is not provided. There is therefore a need in the art to present this information to chemists performing computer implemented molecular modeling in a more user friendly format.
In one embodiment, the invention comprises a method of modeling molecular structure comprising the display of information representative of the physical invalidity of a modeled molecular structure and simultaneously accepting commands from a user to modify the modeled molecular structure.
The invention also comprises apparatus molecular modeling. In one embodiment, such apparatus comprises a display device for outputting a multidimensional representation of a user-defined molecular structure and an input device for receiving user commands to modify the user defined molecular structure. The apparatus further comprises a structure monitor comprising a plurality of validity attributes associated with a respective plurality of atoms of the user-defined molecular structure. The structure monitor is coupled to the display device so as to display information representative of a current status of the plurality of validity attributes. The structure monitor is coupled to the input device such that the current status is modified in response to user commands to modify the molecular structure. Thus, the display of information is updated as the molecular structure is modified by a user.
Another aspect of the invention comprises a computer readable media having instructions stored thereon which configure a general purpose computer to perform a method of molecular modeling comprising the simultaneous performance of (1) displaying information representative of physical invalidity of a molecular model and (2) accepting commands from a user to modify the molecular model.